Pathophysiological Role of Calpain with Special Reference to its Implication in Ischemic Myocardial Injury

Two types of calpain, ubiquitous neutral proteases, requiring μM or mM Ca^<2+> level, are designated as μ-calpain and m-calpain, respectively. Endogenous inhibitor for calpains, calpastatin, plays a regulatory role in calpain activity. In response to the Ca^<2+> transient during platelet activation, μ-calpain translocates from cytosol to membrane fraction where calpain is autolyzed while it degrades Ca^<2+>-ATPase, altering Ca^<2+> homeostasis. Calpastatin remains in the cytosol. In ischemia and reperfusion of rat myocardium, m-calpain activity that was associated with membrane fraction increased with the degradation of several calpain substrate including fodrin. Fodrin associated actin filaments with plasma membrane to maintain the integrity of the cell. The proteolysis of fodrin by calpain would initiate irreversible injury (infarction) in ischemic myocardium as well as in brain. Some specific antibody, which recognize activated form of calpain or degraded form of fodrin, have been recently developed and successfully applied to immunohistochemical studies. This approach will give significant insight into the pathophysiological role of calpain and will be utilized in the specific diagnosis. Several calpain substrate were demonstrated in the brain lesion of Arzheimer's disease. Many researchers now pay attension to the pathophysiological role of calpain.

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